1. Field of the Invention
The invention relates to 2'-alkylsulfonylsteroido[2,3-d]oxazoles, which are useful as antiandrogenic agents, and processes for preparation, method of use and compositions thereof.
2. Information Disclosure Statement
Christiansen et al. U.S. Pat. No. 4,684,636 issued Aug. 4, 1987 describes antiandrogenic sulfonylsteroidopyrazoles including as EXAMPLE 1 the compound having the structural formula ##STR1## which showed relative binding affinities of 2.1 at 1 hr. and 0.09 at 18 hr. in the rat prostate androgen receptor competition assay and an AED.sub.50 value of 14 mg./kg. orally in the test for antiandrogenic activity in the castrated immature male rat.
Babcock et al. U.S. Pat. No. 4,297,350 issued Oct. 27, 1981 describes a series of steroido[2,3-d]oxazoles having the structural formula ##STR2## wherein R.sub.2.alpha. is hydrogen, alkyl of one to four carbon atoms or benzyl, R.sub.6 is hydrogen or methyl, R.sub.7 is hydrogen or methyl, R.sub.17.alpha. is hydrogen, alkyl of one to four carbon atoms, alkenyl of two to four carbon atoms or alkynyl of two to four carbon atoms, R.sub.17.beta. is hydrogen, alkyl of one to four carbon atoms, alkenyl of two to four carbon atoms, ##STR3## --(CH.sub.2).sub.n --CH(CH.sub.2).sub.m, --CH.sub.2 --alkenyl wherein alkenyl has two to fifteen carbon atoms or --CH.sub.2 --C.tbd.CH, R.sub.17.alpha. and R.sub.17.beta. can be connected to form a cyclic ether of four or five carbon atoms, M is hydrogen, methyl, methoxy, trifluoromethyl, hydroxy, nitro, fluoro, chloro or bromo, m is 4-6, n is 0-4, q is 1-2 and wherein when q is 2 the M's can be the same or different and allegedly having utility as male contraceptives.
Omar et al. (Journal of Pharmaceutical Sciences, vol. 73, pp. 1871-1873, 1984) describes the 2'-thiosteroido[2,3-d]oxazoline having the following structural formula but does not describe an biological property thereof. ##STR4##
Ibrahim et al. (Journal of Heterocyclic Chemistry, vol. 19, pp. 761-768, 1982) describes a series of 2'-(substituted amino)steroido[2,3-d]oxazoles having the structural formula ##STR5## wherein R is cyclohexyl, benzyl, phenyl, 3- and 4-methylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl and 4-bromophenyl. The reference states that the compounds were tested "for in vitro anabolic-catabolic activities by measuring their effects on the activity of bovine pancreatic ribonuclease" and shown "to possess almost the same percentage activation as that induced by estrone on the enzyme".
Wolloch et al. (Tetrahedron, vol. 32, pp. 1289-1292, 1976) describes2'-methyl-5.alpha.-cholest-2-eno[2,3-d]isoxazolebut does not describe any biological property thereof.
Crabbe et al. (Tetrahedron, vol, 27 pp. 711-725, 1971) describes 2' methyl-estra-1(10),2,4-trieno[2,3-d]oxazol-17.beta.-ol acetate ester but does not describe any biological property thereof
Ohta et al. (Chemical and Pharmaceutical Bulletin, vol, 16, pp. 1487'1497, 1968) describes 2'-methyl-5.alpha.-androst-2-eno [2,3-d]oxazol-17.beta.-ol and the acetate ester thereof and 2'-methyl-5.alpha.-cholest-2-eno[2,3-d]oxazole. Concerning the androstane derivatives the reference states only that they "revealed considerably diminished activities when compared with testosterone propionate given by subcutaneous injection." No statement is made concerning any biological property of the cholestane derivative.